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Fecal exosomes as a source of miRNA biomarkers for diagnosing the degree of colitis and as a drug delivery system to reduce colitis

Award Number: R01DK116306
ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Summary In addition to secreting soluble mediators, colonic epithelial cells also secrete exosomes (a type of nanovesicle) that contain epigenetic material (proteins, transcription factors, RNAs, miRNAs and DNA fragments). Exosomes are thought to be released basolaterally into the mucosa, where they may regulate local innate responses, and apically, where they may functionally modulate cells at a distance along the gastrointestinal tract and regulate the homeostasis of gut microbiota. In the proposed work, we will exclusively focus on the apical secretion of exosomes into the lumen. Our preliminary results demonstrate that exosomes secreted into the lumen by colonic epithelial cells transit along the gastrointestinal tract and are present in feces. Importantly, colonic and fecal exosomes are similar in their sizes (~140 nm) and miRNA compositions, suggesting that exosomes protect the loaded epigenetic material from highly destructive elements, such as the catabolic enzymes found in the gastrointestinal lumen. Our central hypothesis is that fecal exosomes could yield new miRNA biomarker signatures that may be used to diagnose the degree of colitis and as a drug delivery system to reduce colitis. Our first aim will be to examine the effects of colitis on fecal exosomes, with the aim of identifying new miRNAs that may be used as an intestinal biomarker signature that reflects disease severity. In Aim 2, we will examine whether the microbiota composition can be modulated by the administration of various miRNA panels. In Aim 3, we will examine whether orally administered autologous-healthy fecal exosomes, either alone or as a drug carrier, can reduce intestinal inflammation. It is envisaged that the proposed experiments will facilitate the identification of new biomarkers signatures for intestinal inflammation and allow the development of new therapeutic strategies.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2023 ( Subtotal = $0 )
2023	2020	GEORGIA STATE UNIVERSITY RESEARCH FOUNDATION INC	58 EDGEWOOD AVE NE	ATLANTA	GA	30303	FULTON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	4	6/13/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $0 )
2022	2020	GEORGIA STATE UNIVERSITY RESEARCH FOUNDATION, INC.	58 EDGEWOOD AVE NE 3RD FL	ATLANTA	GA	30303	FULTON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	4	6/10/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2020 ( Subtotal = $445,024 )
2020	2020	GEORGIA STATE UNIVERSITY RESEARCH FOUNDATION, INC.	58 EDGEWOOD AVE NE 3RD FL	ATLANTA	GA	30303	FULTON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	4	7/16/2020	NON-COMPETING CONTINUATION	$445,024
														Subtotal = $445,024

Issue Date FY: 2019 ( Subtotal = $445,024 )
2019	2019	GEORGIA STATE UNIVERSITY RESEARCH FOUNDATION, INC.	58 EDGEWOOD AVE NE 3RD FL	ATLANTA	GA	30303	FULTON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	3	7/23/2019	NON-COMPETING CONTINUATION	$445,024
														Subtotal = $445,024

Issue Date FY: 2018 ( Subtotal = $445,024 )
2018	2018	GEORGIA STATE UNIVERSITY RESEARCH FOUNDATION, INC.	58 EDGEWOOD AVE NE 3RD FL	ATLANTA	GA	30303	FULTON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	7/25/2018	NON-COMPETING CONTINUATION	$445,024
														Subtotal = $445,024

Issue Date FY: 2017 ( Subtotal = $445,024 )
2017	2017	GEORGIA STATE UNIVERSITY RESEARCH FOUNDATION, INC.	58 EDGEWOOD AVE NE 3RD FL	ATLANTA	GA	30303	FULTON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	9/20/2017	NEW	$445,024
														Subtotal = $445,024

Grand Total All Awards = $1,780,096

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Fecal exosomes as a source of miRNA biomarkers for diagnosing the degree of colitis and as a drug delivery system to reduce colitis

Award Number: R01DK116306

ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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